Functional organization of extracellular hyaluronan, CD44, and RHAMM
Bibliographic record
Abstract
Abstract The integral membrane protein CD44 is constitutively expressed in most tissues, and is the primary cell surface receptor for hyaluronan (HA). HA is the key scaffolding organizer of proteoglycans and receptors in the extracellular matrix. CD44 is expressed as cell type‐specific and context‐specific alternatively spliced isoforms with variable glycosylation and interreceptor interactions. CD44 plays a critical role in the organization and patterning of domains in the cell membrane, achieved through linking the cortical actin cytoskeleton with the pericellular HA matrix. This functional and spatial organization of CD44 and HA maintains a protective and homeostatic cellular microenvironment. Tissue injury and cellular stress result in HA fragmentation and unconventional export of the CD44 coreceptor, RHAMM, which collectively alter the homeostatic organization of CD44/HA. The resulting interplay among HA, HA fragments, CD44 and RHAMM triggers cellular responses such as cell motility that contribute to tissue repair, and disease processes. Here we review current understanding of the structural biology of HA, CD44, and RHAMM, and provide an overview of their known functional organization and patterning at the cell surface. Changes in their surface organization act as sensors for detecting danger, and are critical to the understanding of consequent intracellular signaling and response mechanisms to cellular stress.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".